Fluarix

SIDE EFFECTS

Clinical Trials Experience

Because clinical trials are conducted under widely
varying conditions, adverse reaction rates observed in the clinical trials of a
vaccine cannot be directly compared to rates in the clinical trials of another
vaccine, and may not reflect the rates observed in practice. There is the possibility
that broad use of FLUARIX could reveal adverse reactions not observed in
clinical trials.

Adults

In adults, the most common ( ≥ 10%) local adverse
reactions and general adverse events observed with FLUARIX were pain and
redness at the injection site, muscle aches, fatigue, and headache.

FLUARIX has been administered to 10,317 adults 18 through
64 years of age and 606 subjects 65 years of age and older in 4 clinical
trials.

One of the 4 clinical trials was a randomized,
double-blind, placebo-controlled study that evaluated a total of 952 subjects:
FLUARIX (N = 760) and placebo (N = 192). The population was 18 through 64 years
of age (mean 39.1), 54% were female and 80% were white. Solicited events were
collected for 4 days (day of vaccination and the next 3 days) (Table 2).
Unsolicited events that occurred within 21 days of vaccination (day 0-20) were
recorded using diary cards supplemented by spontaneous reports and a medical
history as reported by subjects.

Table 2: Incidence of Solicited Local Adverse
Reactions or General Adverse Events Within 4 Daysa of Vaccination in
Adults 18 Through 64 Years of Ageb (Total Vaccinated Cohort)

FLUARIX
N = 760 %

Placebo
N = 192 %

Local Adverse Reactions

Pain

55

12

Redness

18

10

Swelling

9

6

General Adverse Events

Muscle aches

23

12

Fatigue

20

18

Headache

19

21

Arthralgia

6

6

Shivering

3

3

Fever ≥ 100.4°F (38.0°C)

2

2

Total vaccinated cohort for safety included all
vaccinated subjects for whom safety data were available.a 4 days included day of vaccination and the subsequent 3 days.b NCT00100399.

A randomized, single-blind, active-controlled US study
evaluated subjects randomized to receive FLUARIX (N = 917) or FLUZONE (N =
910), a US-licensed trivalent, inactivated influenza vaccine (Sanofi Pasteur
SA) stratified by age: 18 through 64 years and 65 years of age and older. In
the overall population, 59% of subjects were female and 91% were white.
Solicited events were collected using diary cards for 4 days (day of
vaccination and the next 3 days) (Table 3). Unsolicited events that occurred
within 21 days of vaccination (day 0-20) were recorded using diary cards.

Table 3 : Incidence of Solicited Local Adverse Reactions
or General Adverse Events in Adults Within 4 Daysa of Vaccination
With FLUARIX or Comparator Influenza Vaccine by Age Groupb (Total
Vaccinated Cohort)

18 Through 64 Years of Age

65 Years of Age and Older

FLUARIX
N = 315 %

Comparator Influenza Vaccine
N = 314 %

FLUARIX
N = 601-602 %

Comparator Influenza Vaccine
N = 596 %

Local Adverse Reactions

Pain

48

53

19

18

Redness

13

16

11

13

Swelling

9

11

6

9

General Adverse Events

Fatigue

21

18

9

10

Headache

20

21

8

8

Muscle aches

16

13

7

7

Arthralgia

9

9

6

5

Shivering

3

5

2

2

Fever ≥ 99.5 °F (37.5°C)

3

1

2

1

Total vaccinated cohort for safety included all vaccinated
subjects for whom safety data were available.a 4 days included day of vaccination and the subsequent 3 days.b NCT00197288.

A double-blind, placebo-controlled study in subjects 18
through 64 years of age randomized (2:1) to receive FLUARIX (N = 5,103) or
placebo (N = 2,549) was conducted to evaluate the efficacy of FLUARIX. In the
total population, 60% were female and 99.9% were white. In a subset (FLUARIX [N
= 305] and placebo [N = 155]), unsolicited events that occurred within 21 days
of vaccination (day 0-20) were recorded on diary cards. The percentage of subjects
reporting at least one unsolicited event was similar among the groups (24.3%
for FLUARIX and 22.6% for placebo). Unsolicited adverse events that occurred in
≥ 1% of recipients of FLUARIX and at a rate greater than placebo included
injection site pain (5.2% versus 1.3%), dysmenorrhea (1.3% versus 0.6%), and
migraine (1.0% versus 0.0%).

Incidence of Adverse Events Reported in ≥ 1% of
Subjects in Non-US Clinical Trials: The following additional adverse events
have been observed in adults in non-US clinical trials with FLUARIX. No adverse
events were observed at an incidence of > 10%.

Serious Adverse Events: In the 4 clinical trials
in adults (N = 10,923), there was a single case of anaphylaxis reported with
FLUARIX ( < 0.01%).

Children

In children 5 years through 17 years of age, the most
common ( ≥ 10%) local and general adverse events were similar to those in
adults but also included swelling at the injection site. In children 3 years
through 4 years of age, the most common ( ≥ 10%) local and general adverse
events included pain, redness, and swelling at the injection site,
irritability, loss of appetite, and drowsiness.

A single-blind, active-controlled US study evaluated
subjects 6 months through 17 years of age who received FLUARIX (N = 2,081) or
FLUZONE (N = 1,173), a US-licensed trivalent, inactivated influenza vaccine
(Sanofi Pasteur SA) (Study 005). Children 6 months through 8 years of age with
no history of influenza vaccination received 2 doses approximately 28 days apart.
Children 6 months through 8 years of age with a history of influenza
vaccination and children 9 years of age and older received 1 dose. Children 6
months through 35 months of age received 0.25 mL of FLUARIX or comparator
influenza vaccine, and children 3 years of age and older received 0.5 mL of
FLUARIX or comparator influenza vaccine.

Study subjects were 6 months through 17 years of age and
49% were female; 68% were white, 18% were black, 3% were Asian, and 11% were of
other racial/ethnic groups.

Solicited local and general adverse events were collected
using diary cards for 4 days (day of vaccination and the next 3 days).
Unsolicited adverse events that occurred within 28 days of vaccination (day
0-27) after the first vaccination in all subjects and 21 days (day 0-20) after the
second vaccination in unprimed subjects were recorded using diary cards.

The frequencies of solicited adverse events for children
3 years through 4 years of age and for children 5 years through 17 years of age
were similar for FLUARIX and the comparator vaccine (Table 4).

Table 4: Incidence of Solicited Local Adverse
Reactions or General Adverse Events Within 4 Daysa of First
Vaccination With FLUARIX or Comparator Influenza Vaccine by Age Group in
Children 3 Through 17 Years of Ageb

3 Through 4 Years of Age

5 Through 17 Years of Age

FLUARIX
N = 350 %

Comparator Influenza Vaccine
N = 341 %

FLUARIX
N = 1,348 %

Comparator Influenza Vaccine
N = 451 %

Local Adverse Reactions

Pain

35

38

56

56

Redness

23

20

18

16

Swelling

14

13

14

13

General Adverse Events

Irritability

21

22

-

-

Loss of appetite

13

15

-

-

Drowsiness

13

20

-

-

Fever ≥ 99.5 °F (37.5°C)

7

8

4

3

Muscle aches

-

-

29

29

Fatigue

-

-

20

19

Headache

-

-

15

16

Arthralgia

-

-

6

6

Shivering

-

-

3

4

a 4 days included day of vaccination and the
subsequent 3 days.b NCT00383123.

In children who received a second dose of FLUARIX or the
comparator vaccine, the incidences of adverse events following the second dose
were similar to those observed after the first dose.

Postmarketing Experience

Worldwide voluntary reports of adverse events received
for FLUARIX since market introduction of this vaccine are listed below. This
list includes serious events or events which have causal connection to FLUARIX.
Because these events are reported voluntarily from a population of uncertain
size, it is not always possible to reliably estimate their frequency or establish
a causal relationship to the vaccine.

DRUG INTERACTIONS

Concomitant Vaccine Administration

FLUARIX should not be mixed with any other vaccine in the
same syringe or vial.

There are insufficient data to assess the concurrent
administration of FLUARIX with other vaccines. When concomitant administration
of other vaccines is required, the vaccines should be administered at different
injection sites.